Tools
Cardiac Biomarkers
Introduction
Cardiac biomarkers are endogenous substances released into the bloodstream when the heart muscle is damaged or stressed.[1] Measurement of these biomarkers is used to help diagnose, risk-stratify, and guide treatment for acute coronary syndrome, a potentially life-threatening condition characterized by the sudden onset of persistent pain in the chest, 1 or both arms, shoulders, abdomen, or jaw, as well as shortness of breath, nausea, sweating, and dizziness.[2]
Cardiac biomarkers have been used since the mid-20th century to evaluate patients with suspected acute myocardial infarction. The biomarkers used previously are no longer clinically relevant because more sensitive and specific biomarkers have replaced them.[3] Troponins are the primary cardiac biomarkers used in clinical practice to diagnose acute myocardial infarction.[4] In contrast to creatine kinase, whose levels usually increase 6 to 12 hours after emergency department presentation, troponin levels are elevated in most cases of acute myocardial infarction within 2 to 3 hours of arrival.[5]
Beyond troponins, several other biomarkers play important supporting roles. Myoglobin can help detect early myocardial injury, while natriuretic peptides are widely used to assess heart failure. In addition, newer markers such as copeptin, soluble suppression of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor 15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP) contribute to early diagnosis, risk stratification, and prognostic assessment across a broad range of cardiovascular conditions.
Specimen Requirements and Procedure
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Specimen Requirements and Procedure
Accurate measurement of contemporary cardiac biomarkers requires strict attention to specimen type, anticoagulant selection, processing time, and storage conditions, because preanalytical variability can significantly influence interpretation, particularly when serial measurements are used to diagnose acute myocardial infarction or detect reinfarction.[6] For cardiac troponins, including high-sensitivity cardiac troponin, serum and heparinized plasma (lithium heparin preferred over sodium heparin to avoid rare cation interference) are the most commonly accepted specimen types for most commercially available assays.[7] Additionally, certain point-of-care platforms permit whole blood testing.[8] However, clinically relevant differences have been reported between serum and plasma, particularly for cardiac troponin I, with plasma values in some assay systems measuring up to 30% lower than corresponding serum concentrations. These matrix-related differences necessitate strict consistency in specimen type during serial monitoring and validation, as recommended by the manufacturer.[9]
In patients receiving anticoagulant therapy, delayed clot formation may affect serum preparation, and inadequate clotting before centrifugation can lead to fibrin interference. Conversely, plasma samples may yield relatively lower measured concentrations, which could theoretically reduce sensitivity for detecting small or evolving infarctions in early presentations, particularly those near the 99th percentile upper reference limit.[10] Prompt centrifugation and separation from cells are essential, ideally within 2 hours, and specimens should be analyzed rapidly or stored at 2 °C to 8 °C for short-term preservation; for longer storage, freezing at −20 °C or, preferably, −70 °C to −80 °C is recommended, depending on assay specifications. Hemolysis, lipemia, and icterus should be minimized because significant hemolysis may interfere with certain immunoassay platforms, particularly high-sensitivity assays that rely on detecting very low analyte concentrations.[11][12]
For creatine kinase and creatine kinase MB (CK-MB) isoenzyme, serum or heparinized plasma, with lithium heparin preferred, is an acceptable specimen type. Anticoagulants other than heparin, such as thylenediaminetetraacetic acid (EDTA), citrate, or oxalate, should be avoided because they inhibit creatine kinase enzymatic activity and may result in falsely low measurements.[13] Gel separator tubes generally do not significantly affect creatine kinase activity.[14] Creatine kinase is relatively unstable compared with immunoassay-based biomarkers; it typically remains stable for less than 8 hours at room temperature and up to 48 hours at 2 °C to 8 °C, while longer storage requires freezing, preferably at −80 °C if analysis is substantially delayed.[14][15] Fresh, nonhemolyzed serum is preferred for creatinine kinase isoenzyme analysis because hemolysis and prolonged storage may reduce enzyme activity and compromise interpretation.[16]
Myoglobin measurement requires a nonhemolyzed, nonlipemic specimen, most commonly serum. Results from some studies have shown comparable values between serum and heparinized plasma; however, EDTA plasma has been associated with significantly lower values in certain assay systems, and various anticoagulants may interfere with immunoassay performance. Because myoglobin rises and falls rapidly following myocardial injury, prompt specimen processing is critical to preserve diagnostic sensitivity.[17][18] Samples should be centrifuged without delay and refrigerated if analyzed within 24 hours; otherwise, freezing at −20 °C or preferably −80 °C is recommended.[19]
For natriuretic peptides, which are primarily used in heart failure diagnosis and risk stratification rather than acute infarction diagnosis, specimen requirements differ slightly. B-type natriuretic peptide (BNP) is best measured in EDTA plasma because this biomarker is less stable in serum and susceptible to proteolytic degradation; prompt processing and cooling are important to maintain accuracy.[20] In contrast, N-terminal pro–B-type natriuretic peptide (NT-proBNP) is more stable and may be measured in serum or plasma depending on assay specifications, with acceptable stability for several days at 2 °C to 8 °C and longer when frozen.[21] Other prognostic biomarkers such as copeptin, sST2, galectin-3, GDF-15, and hs-CRP are typically measured in serum or EDTA plasma, and laboratories must adhere strictly to manufacturer-specific recommendations regarding anticoagulant type, processing time, and storage conditions to minimize analytical variability.[22][23][24] Overall, consistent specimen selection, avoidance of hemolysis, prompt centrifugation, and adherence to validated storage protocols are essential to ensure analytical reliability, particularly in the era of high-sensitivity troponin assays, where clinical decision-making depends on detecting small but clinically meaningful dynamic changes.[25]
Diagnostic Tests
Aspartate aminotransferase (AST) was the first biomarker used to diagnose acute myocardial infarction (AMI). In 1954, Ladue et al proposed that AST released from necrotic cardiomyocytes could assist in diagnosing AMI.[26] AST increases in the blood 3 to 4 hours after an infarction, peaks at 15 to 28 hours, and returns to baseline within approximately 5 days. However, AST lacks cardiac specificity because elevated levels may also occur in hepatic disease (eg, hepatitis or hepatic congestion), pericarditis, pulmonary embolism, and shock. Consequently, AST is no longer used in diagnosing AMI.[27][28]
Following the identification of AST release from ischemic myocardium, lactate dehydrogenase (LDH) emerged as another biomarker for myocardial injury. Total LDH increases 6 to 12 hours after AMI, peaks within 24 to 72 hours, and normalizes within 8 to 14 days. Historically, an LDH-1 to LDH-2 ratio greater than 1, known as the LDH flip, was considered suggestive of myocardial infarction.[29] However, due to poor cardiac specificity and elevations in numerous other conditions, LDH has become obsolete for diagnosing and timing AMI in the era of high-sensitivity troponin assays. Currently, LDH retains clinical value primarily in detecting hemolysis and in oncologic applications, such as monitoring testicular germ cell tumors.[30]
Myoglobin, a heme protein found in cardiac and skeletal muscle, was introduced as an early biomarker. Owing to its small molecular size, myoglobin can be detected in the blood as early as 1 hour after myocardial injury, peaks within 4 to 12 hours, and rapidly returns to baseline.[31] Although its early rise offered a diagnostic advantage, myoglobin’s poor specificity for cardiac tissue limited its utility. Troponins have largely replaced myoglobin for diagnosing AMI; however, myoglobin remains useful for assessing skeletal muscle injury and rhabdomyolysis.[32]
Heart-type fatty acid-binding protein (H-FABP) is involved in fatty acid metabolism in cardiac myocytes. In results from a study by Kabekkodu et al, the sensitivity of H-FABP in detecting AMI in patients who present within 4 hours of symptom onset was 60%, which was significantly higher than that of troponin (18.8%) and CK-MB (12.5%). The sensitivity of H-FABP in detecting AMI between 4 and 12 hours after symptom onset was 86.96%, comparable to troponin (90.9%) and higher than CK-MB (77.3%).[33] However, the specificity of H-FABP in detecting AMI was less than that of troponin and CK-MB.[34] Despite its high sensitivity for detecting myocardial ischemia, H-FABP is not used clinically in the US and has not undergone rigorous comparison with high-sensitivity cardiac troponin T assays. Thus, H-FABP is unsuitable as a standalone test for diagnosing AMI but may have some value as an adjunctive test in specific patient populations.[35]
Creatine kinase MB subsequently became a widely used cardiac biomarker. CK-MB rises approximately 4 hours after myocardial injury, peaks at 24 hours, and returns to baseline within 48 to 72 hours.[36] Although relatively more cardiac-specific than earlier markers, CK-MB can be elevated in skeletal muscle injury, hypothyroidism, chronic renal failure, and intense exercise.[37] The CK-MB relative index is calculated as follows:
(CK-MB)/total CK × 100,
and CK-MB2 to CK-MB1 ratios were used to improve specificity.[38] In contemporary practice, CK-MB has largely been replaced by high-sensitivity cardiac troponins but may retain limited value in detecting reinfarction when troponin assays are unavailable.[36]
Cardiac troponins are now the gold standard biomarkers for diagnosing AMI. Troponin is a regulatory protein complex composed of troponin C, troponin I, and troponin T. Cardiac troponin I and cardiac troponin T are structurally distinct from skeletal isoforms, conferring high specificity for myocardial injury.[39] Troponin levels begin to rise within 3 to 4 hours after symptom onset, peak at 24 to 48 hours, and may remain elevated for 7 to 14 days (cardiac troponin T up to 14 days; cardiac troponin I often 7 to 10 days).[40] High-sensitivity cardiac troponin assays detect troponin concentrations at much lower levels with improved precision, enabling earlier diagnosis and rapid rule-in or rule-out algorithms within 1 to 3 hours of presentation. Additionally, high-sensitivity cardiac troponin assays enable identification of reinfarction by demonstrating significant dynamic changes, typically greater than 20%, in serial measurements when baseline values are already elevated. Although high-sensitivity cardiac troponin assays exhibit very high sensitivity and negative predictive value, specificity may be limited because troponin elevations can also occur in myocarditis, heart failure, renal failure, pulmonary embolism, and sepsis.[7][41] The modern definition of myocardial infarction, endorsed by the European Society of Cardiology and the American College of Cardiology in the Fourth Universal Definition of Myocardial Infarction (2018), requires a rise and fall in cardiac troponin values with at least 1 value above the 99th percentile upper reference limit, accompanied by clinical evidence of myocardial ischemia, including symptoms, electrocardiographic changes, imaging evidence, or identification of coronary thrombus.[42]
Beyond biomarkers of myocardial necrosis, contemporary cardiac biomarkers serve important roles in risk stratification, heart failure diagnosis, and prognostication. B-type natriuretic peptide and NT-proBNP are released in response to ventricular wall stress and are central to diagnosing and monitoring heart failure.[43] Copeptin, the C-terminal fragment of provasopressin, rises rapidly in response to endogenous stress and AMI and has been studied as an adjunct to troponin for early rule-out of AMI.[44] Soluble ST2 and galectin-3 are biomarkers associated with myocardial fibrosis and remodeling, providing prognostic value in heart failure.[45] Growth differentiation factor-15 reflects oxidative stress and inflammation and adds incremental prognostic information in acute coronary syndromes.[46] High-sensitivity C-reactive protein is widely used for cardiovascular risk assessment as an indicator of vascular inflammation, while lipoprotein(a) and apolipoprotein B, and apolipoprotein A1 contribute to long-term atherosclerotic cardiovascular risk stratification rather than acute infarction diagnosis.[47]
In modern clinical practice, high-sensitivity cardiac troponin is the gold-standard biomarker for diagnosing AMI. In contrast, natriuretic peptides, sST2, galectin-3, GDF-15, and hs-CRP are mainly used for prognostication and risk stratification. Emerging biomarkers such as copeptin and H-FABP may offer additional diagnostic support in selected patient populations; however, they do not replace troponins in diagnosing AMI.[48]
Testing Procedures
Several troponin assays are commercially available, including high-sensitivity cardiac troponin and conventional assays. Current assays for cardiac troponin T and cardiac troponin I are typically 2- or 3-site immunoassays.[49] In these capture assays, a specific immobilized antibody binds to troponin in the serum or plasma sample. A second antibody, and in some assays a third antibody, conjugated to an indicator molecule, binds to a separate epitope on the captured troponin. The assays differ in antibody specificity, targeted epitopes, and indicator type, such as chemiluminescent, fluorescent, or colorimetric.[50]
Quantitative and semiquantitative point-of-care methods have also been developed, allowing rapid bedside measurement in emergency settings with reasonable precision. High-sensitivity troponin assays can detect troponin at much lower concentrations than conventional assays, enabling early diagnosis of acute myocardial infarction and assessment of reinfarction using serial delta troponin measurements.[50]
CK-MB is primarily measured using immunoinhibition or mass assays. Immunoinhibition methods use antibodies to block the M or B subunit, allowing specific measurement of CK-MB. Mass assays directly quantify the CK-MB isoenzyme using immunoassays, providing better specificity for myocardial injury. CK-MB can also be measured using automated analyzers in clinical laboratories or as part of rapid point-of-care panels, particularly in settings where troponin assays are not available. Please see StatPearls' companion reference, "Creatine Kinase MB: Diagnostic Utility and Limitations," for further information.
Serum myoglobin is determined almost exclusively by immunoassay techniques due to their high analytical sensitivity, specificity, precision, and rapid turnaround time.[51] Radioimmunoassays have historically been used for quantitative measurement, but automated 2-site nonisotopic immunoassays have largely replaced radioimmunoassays in routine practice.[52] Qualitative and quantitative point-of-care tests for myoglobin are also available, allowing rapid early detection of myocardial injury or skeletal muscle damage, although myoglobin lacks cardiac specificity.[53]
H-FABP is measured using immunoassay techniques similar to troponin, including enzyme-linked immunosorbent assay (ELISA) and automated chemiluminescent methods.[54] Rapid point of care assays have been developed to detect H-FABP within the first few hours of myocardial injury. Although these tests are highly sensitive, lower specificity compared with troponin limits their standalone diagnostic use; H-FABP may be applied as an adjunctive biomarker in early presentations.[55]
BNP and NT-proBNP are measured using sandwich immunoassays, typically on automated analyzers. The assays use 2 antibodies targeting different epitopes on the peptide.[56] Point-of-care BNP tests are available, enabling rapid assessment of heart failure severity in emergency or outpatient settings. Analytical considerations include sample type (plasma versus serum), renal function, and acute versus chronic heart failure status.[57]
sST2 and galectin-3 are measured using ELISA and automated immunoassay platforms. They are primarily used for risk stratification in heart failure and are not diagnostic for AMI.[58] GDF-15 and hs-CRP are measured using immunoassays, providing prognostic information for acute coronary syndromes and long-term cardiovascular risk.[59] Copeptin is measured by immunoassay and can serve as an adjunct to troponin for early rule-out of AMI in very early presentations.[60] Lipoprotein(a) is measured using immunoturbidimetric or ELISA methods and is used for long-term atherosclerotic cardiovascular risk assessment rather than acute myocardial injury.[61] Overall, immunoassay-based methods remain the cornerstone for measuring cardiac biomarkers in both central laboratory and point-of-care settings. High-sensitivity troponins continue to serve as the gold standard for diagnosing AMI, whereas other biomarkers, such as CK-MB, myoglobin, H-FABP, natriuretic peptides, and newer markers, offer complementary roles in diagnosis, prognosis, and risk stratification.[62]
Interfering Factors
Cardiac biomarker assays, while highly sensitive and specific, can be influenced by physiologic, pathological, and preanalytical factors, potentially yielding falsely elevated or decreased results.[6] Cardiac troponin testing is the standard, first-line blood test for diagnosing acute myocardial infarction; however, elevations may occur in conditions unrelated to acute coronary ischemia.[63] Cardiac troponin levels can rise after open heart surgical procedures, percutaneous coronary interventions, acute pulmonary embolism, end-stage renal disease, pericarditis, myocarditis, Stanford type A aortic dissection, acute or chronic heart failure, strenuous exercise, cardiotoxic chemotherapy, radiofrequency catheter ablation of arrhythmias, cardioversion of atrial fibrillation or flutter, defibrillation for ventricular arrhythmias, amyloidosis, cardiac contusion from blunt chest trauma, sepsis, and rhabdomyolysis.[64]
Additional conditions reported to be associated with troponin elevation include aortic valve disease, apical ballooning syndrome, Takotsubo cardiomyopathy, bradyarrhythmias, endomyocardial biopsy, hypertrophic cardiomyopathy, tachyarrhythmias, and noncardiac causes such as acute pulmonary edema, chronic obstructive pulmonary disease, pulmonary hypertension, stroke, and subarachnoid hemorrhage.[38] These elevations often reflect a mismatch between myocardial oxygen supply and demand rather than primary coronary artery disease.[64] CK-MB measurements may be affected by skeletal muscle injury, hypothyroidism, chronic renal failure, and intense exercise, leading to false elevations.[65] Hemolysis can interfere with CK-MB and creatine kinase assays by releasing intracellular enzymes and metabolites that alter assay kinetics.[66]
Myoglobin levels are particularly sensitive to preanalytical variables: collection tubes with separator gels, including serum and plasma tubes, can increase or decrease measured levels, and hemolysis or hyperbilirubinemia may affect assay accuracy.[66] Furthermore, H-FABP can be influenced by renal dysfunction and skeletal muscle injury, potentially leading to nonspecific elevations.[67] Natriuretic peptides (BNP, NT-proBNP) are affected by age, sex, body mass index, renal function, and atrial arrhythmias, which may alter their prognostic and diagnostic interpretation.[68] Similarly, sST2, galectin-3, and GDF-15 levels can be influenced by comorbidities such as chronic kidney disease, systemic inflammation, and liver dysfunction.[22]
Copeptin measurements may be affected by stress, dehydration, and other endocrine disorders, while high-sensitivity C-reactive protein is a nonspecific marker of inflammation and can rise in infections, autoimmune conditions, and tissue injury.[69][70] Preanalytical factors, including hemolysis, lipemia, icterus, improper sample handling, delayed processing, and incorrect storage conditions, can affect most cardiac biomarker assays. While moderate hemolysis, with hemoglobin up to 0.32 g/dL, does not significantly affect creatine kinase activity, severe hemolysis releases intracellular contents, such as adenylate kinase, adenosine triphosphate, and glucose-6-phosphate, which may interfere with enzymatic reactions. Turbid or icteric samples can usually be analyzed, provided that the initial absorbance does not exceed assay tolerances. Careful sample collection, prompt processing, and awareness of clinical and comorbid conditions are essential to ensure accurate interpretation of cardiac biomarker results.[71][72]
Results, Reporting, and Critical Findings
Current European Society of Cardiology, American College of Cardiology, and American Heart Association guidelines recommend that cardiac troponin testing be available 24 hours a day, 7 days a week, in all hospitals treating acute coronary syndromes, with a target turnaround time of 30 to 60 minutes from sample collection to result availability to facilitate rapid clinical decision-making in suspected acute myocardial infarction.[73][74] Troponin remains the gold standard biomarker for myocardial injury due to its unmatched cardiac specificity and sensitivity across the full spectrum of myocardial necrosis, with elevated levels not only confirming myocardial necrosis but also providing critical prognostic information.[75] Higher peak concentrations correlate with increased risk of 30-day and 1-year adverse cardiovascular events, including reinfarction, acute heart failure, cardiogenic shock, and mortality.[76]
Serial measurements at 0 and 1 hour, 0 and 3 hours, or 0 and 6 hours are essential to detect significant rise and fall, or Δ troponin, patterns that distinguish acute myocardial infarction, defined by a greater than 20% change when baseline values are elevated or an absolute change greater than 5 to 7 ng/L when baseline values are normal, from chronic stable elevations, defined by less than 20% change, or reinfarction, defined by a new significant rise. High-sensitivity cardiac troponin I and high-sensitivity cardiac troponin T assays enable earlier detection within 1 to 3 hours of symptom onset, rapid rule-in and rule-out algorithms, and lower assay imprecision at the 99th percentile upper reference limit.[77][78]
Complementary prognostic biomarkers include natriuretic peptides, such as BNP or NT-proBNP, which reflect ventricular wall stress and are integral to heart failure diagnosis, treatment, and mortality prediction. Additional complementary biomarkers include sST2 and galectin-3, which are used to assess myocardial fibrosis and remodeling risk; GDF-15, which reflects oxidative stress and inflammation in acute coronary syndrome prognosis; and copeptin, which reflects the early stress response when combined with high-sensitivity cardiac troponin in 0- and 1-hour rule-out protocols.[22][79]
Markers of systemic inflammation and cardiovascular risk, such as hs-CRP, assess residual inflammatory risk in stable coronary artery disease, while lipoprotein(a) and apolipoproteins, including the apolipoprotein B to apolipoprotein A1 ratio, identify genetic and atherogenic particle risks for long-term primary prevention. Reporting should always integrate analytical thresholds, clinical context, and interfering factors, with standardized protocols that include reference ranges, Δ values, and assay details to enhance interpretability. Critical alerts may include a greater than 50% change within 2 hours or values greater than 10 times the 99th percentile upper reference limit. Critical findings require immediate notification to clinicians per Joint Commission standards, and International Organization for Standardization 15189 laboratories should track turnaround time compliance, delta calculations, and quality metrics to optimize patient care.[80]
Clinical Significance
Both conventional and high-sensitivity troponin assays are available, with high-sensitivity assays approved in the US in 2017. High-sensitivity assays allow earlier detection of myocardial injury, improved risk stratification, and identification of reinfarction through serial measurements and delta analysis. Troponin elevations also provide prognostic information because higher levels correlate with increased risk of adverse cardiac events.[81]
Creatine kinase MB isoenzyme exhibits relative cardiac specificity but should not be used as a first-line diagnostic marker when troponin assays are available. Creatine kinase MB isoenzyme remains clinically useful primarily when troponin testing is unavailable. Unlike troponins, CK-MB isoenzyme levels return to baseline within 48 to 72 hours after acute myocardial infarction, making this biomarker valuable for detecting reinfarction if levels rise again after normalization.[82][83]
Myoglobin, a low molecular weight heme protein, rises rapidly within 1 hour of myocardial injury and peaks within 4 to 12 hours. While myoglobin lacks specificity for cardiac tissue, this biomarker can provide early diagnostic support, particularly when used in conjunction with creatine kinase MB isoenzyme, and remains useful for assessing skeletal muscle injury and rhabdomyolysis.[18] Heart-type fatty acid–binding protein rises early after myocardial injury and demonstrates higher sensitivity than conventional troponin and creatine kinase MB isoenzyme in the first few hours of symptom onset. However, its lower specificity limits clinical use, and heart-type fatty acid–binding protein is primarily considered an adjunctive early biomarker in select patient populations.[35]
B-type natriuretic peptide and NT-proBNP are biomarkers of ventricular wall stress rather than myocardial necrosis. Elevated levels provide diagnostic and prognostic information in patients with acute and chronic heart failure, and help guide therapeutic decisions and risk stratification, but are not used for the acute diagnosis of AMI.[79] Copeptin rises rapidly in response to endogenous stress. When measured alongside troponin, copeptin may facilitate the early rule-out of acute myocardial infarction in very early presenters. Clinical utility is primarily adjunctive and not universally applied.[84]
Soluble ST2 and galectin-3 are markers of myocardial fibrosis and remodeling. Their primary use is prognostic, particularly in patients with heart failure or at risk for adverse remodeling after an acute coronary syndrome. Elevated levels correlate with increased risk of mortality and hospitalization.[45] Growth differentiation factor 15 reflects oxidative stress and inflammation. This biomarker is useful for risk stratification in acute coronary syndromes and for long-term cardiovascular prognosis.[45]
In patients presenting with acute chest pain and ST-segment elevation on electrocardiographic findings, immediate clinical decisions, such as primary percutaneous coronary intervention or thrombolytic therapy, should not be delayed while awaiting cardiac biomarker results. Clinicians must recognize that all cardiac markers, including troponins, may have limited sensitivity in the very early hours of infarction. Prompt intervention based on clinical assessment and electrocardiographic findings remains critical for optimizing outcomes in these patients who are at high-risk.[85]
Quality Control and Lab Safety
Quality control of the analytical examination process monitors the measurement procedure to verify that it meets performance specifications appropriate for patient care or to identify errors that must be corrected.[86] For nonwaived tests, laboratory regulations require, at a minimum, analysis of at least 2 levels of quality control materials once every 24 hours. If necessary, laboratories can assay quality control samples more frequently to ensure accurate results. Quality control samples should be assayed after calibration or analyzer maintenance to verify correct method performance.[87] To minimize quality control when performing tests for which manufacturers’ recommendations are less frequent than those required by the regulatory agency, such as once per month, laboratories can develop an individualized quality control plan that involves performing a risk assessment of potential sources of error in all phases of testing and implementing a quality control plan to reduce the likelihood of errors.[88]
The design of a quality control plan must consider the analytical performance capability of a measurement procedure and the risk of harm to a patient that might occur if an erroneous laboratory test result is used for a clinical care decision. An erroneous laboratory test result is a hazardous condition that may or may not harm a patient, depending on the action or inaction a clinician takes based on the result.[89] The acceptable range and rules for interpreting quality control results are based on the probability of detecting a significant analytical error condition with an acceptably low false alert rate.[88] The desired process control performance characteristics must be established for each measurement before selecting the appropriate quality control rules.[90] Westgard multirules are usually used to evaluate the quality control runs. If a run is declared out of control, laboratory personnel should investigate the system, including the instrument, standards, and controls, to determine the cause of the problem. Analysis should not be performed until the problem has been resolved.[91]
Changing reagent lots can have an unexpected impact on quality control results. Careful evaluation of quality control target values across reagent lots is necessary. Because the matrix-related interaction between a quality control material and a reagent can change with a different reagent lot, quality control results may not be a reliable indicator of a measurement procedure’s performance for patient samples after a reagent lot change.[92] Clinical patient samples are necessary to verify the consistency of results between old and new reagent lots because of the unpredictability of matrix-related bias in quality control materials.[93]
The laboratory must participate in an external quality control or proficiency testing program because participation is a regulatory requirement under the Centers for Medicare and Medicaid Services' Clinical Laboratory Improvement Amendments regulations.[94] Participation helps ensure laboratory accuracy and reliability compared with other laboratories performing the same or comparable assays. Required participation and scored results are monitored by the Centers for Medicare and Medicaid and voluntary accreditation organizations. The proficiency testing plan should be included in the quality assessment plan and the laboratory's overall quality program.[95]
Laboratory personnel should consider all specimens, control materials, and calibrator materials potentially infectious. They should exercise the usual precautions required for handling all laboratory reagents. Disposal of all waste material should be in accordance with local guidelines. Personnel should wear gloves, a lab coat, and safety glasses when handling human blood specimens. All plastic tips, sample cups, and gloves that come into contact with blood should be placed in a biohazard waste container.[96] All disposable glassware should be disposed of in the sharps waste containers. All work surfaces should be protected with disposable absorbent benchtop paper, which should be disposed of in biohazard waste containers weekly or whenever blood contamination occurs. All work surfaces should be wiped weekly.[97]
Enhancing Healthcare Team Outcomes
The effective use of modern cardiovascular biomarkers, such as high-sensitivity troponin, CK-MB in selected cases, myoglobin, BNP and NT-proBNP, and newer markers like copeptin, sST2, galectin-3, GDF-15, and hs-CRP, depends on a coordinated, patient-focused team approach. In daily practice, even small changes in troponin values, particularly around the 99th percentile cutoff, can influence important clinical decisions. Analytical accuracy, appropriate test selection, and timely reporting are therefore essential for safe and effective patient care.
Early recognition of acute myocardial infarction allows prompt initiation of reperfusion therapy, which can limit myocardial damage and improve survival. Beyond diagnosing acute events, biomarkers also play a role in managing chronic conditions. Natriuretic peptides are well established in heart failure diagnosis and follow-up, while markers such as sST2, galectin-3, GDF-15, and hs-CRP provide additional information on risk, inflammation, and long-term prognosis. Using these tests effectively requires close coordination between clinical and laboratory teams.
Clinicians are responsible for selecting appropriate tests and applying recommended diagnostic pathways, including rapid rule-in and rule-out protocols for troponin. Interpretation should always consider the clinical picture, along with electrocardiographic findings and imaging results. Clinicians should also recognize that troponin may be elevated in noncardiac conditions such as myocarditis, renal impairment, or sepsis, and additional biomarkers should be used appropriately when assessing heart failure or risk.
Nurses are often the first to identify symptoms suggestive of cardiac disease and play a key role in ensuring timely sample collection and adherence to clinical pathways. Accurate timing of serial samples, along with proper labeling and handling, is critical to avoid preanalytical errors that may affect results. Within the laboratory, technologists and scientists maintain the reliability of results through quality control, calibration, and participation in external quality programs. Clinical pathologists contribute by providing interpretative guidance, helping define meaningful changes in troponin levels, and supporting the appropriate use of different assays. They also play an important role in standardizing reports and improving laboratory processes through ongoing quality initiatives. Pharmacists add further value by tailoring treatment based on biomarker trends and patient risk. Pharmacist involvement includes optimizing therapies such as antiplatelet and anticoagulant agents, statins, and heart failure medications, while also monitoring for interactions and necessary dose adjustments.
Clear communication across the team is essential. Structured reporting of critical values, electronic alerts, interdisciplinary discussions, and well-defined handovers between departments all help reduce delays and prevent errors. An open working environment that encourages input from nurses, laboratory staff, and pharmacists supports the timely resolution of concerns and strengthens patient safety. Ethical practice involves using these tests thoughtfully to avoid unnecessary investigations or misinterpretation. Patients should be informed about what their results mean and how they guide treatment decisions. Care typically spans multiple stages, from emergency assessment to inpatient care and outpatient follow-up, making coordination at each step important. Standardized protocols and collaborative quality efforts help maintain consistency and accountability. Overall, combining clinical judgment, reliable laboratory data, effective communication, and shared responsibility enables the healthcare team to make the most of cardiac biomarkers. This interprofessional approach ultimately improves patient outcomes and supports high-quality, team-based care.
References
Jacob R, Khan M. Cardiac Biomarkers: What Is and What Can Be. Indian journal of cardiovascular disease in women WINCARS. 2018 Dec:3(4):240-244. doi: 10.1055/s-0039-1679104. Epub [PubMed PMID: 31934672]
O Collinson P. Cardiac markers. British journal of hospital medicine (London, England : 2005). 2009 Jun:70(6):M84-7 [PubMed PMID: 19516200]
Plebani M, Zaninotto M. Cardiac markers: present and future. International journal of clinical & laboratory research. 1999:29(2):56-63 [PubMed PMID: 10436262]
Tiwari RP, Jain A, Khan Z, Kohli V, Bharmal RN, Kartikeyan S, Bisen PS. Cardiac troponins I and T: molecular markers for early diagnosis, prognosis, and accurate triaging of patients with acute myocardial infarction. Molecular diagnosis & therapy. 2012 Dec:16(6):371-81. doi: 10.1007/s40291-012-0011-6. Epub [PubMed PMID: 23184341]
Singh V, Martinezclark P, Pascual M, Shaw ES, O'Neill WW. Cardiac biomarkers - the old and the new: a review. Coronary artery disease. 2010 Jun:21(4):244-56. doi: 10.1097/MCA.0b013e328338cd1f. Epub [PubMed PMID: 20351549]
Cemin R, Daves M. Pre-analytic variability in cardiovascular biomarker testing. Journal of thoracic disease. 2015 Oct:7(10):E395-401. doi: 10.3978/j.issn.2072-1439.2015.10.03. Epub [PubMed PMID: 26623116]
Lazar DR, Lazar FL, Homorodean C, Cainap C, Focsan M, Cainap S, Olinic DM. High-Sensitivity Troponin: A Review on Characteristics, Assessment, and Clinical Implications. Disease markers. 2022:2022():9713326. doi: 10.1155/2022/9713326. Epub 2022 Mar 28 [PubMed PMID: 35371340]
Dominici R, Infusino I, Valente C, Moraschinelli I, Franzini C. Plasma or serum samples: measurements of cardiac troponin T and of other analytes compared. Clinical chemistry and laboratory medicine. 2004:42(8):945-51 [PubMed PMID: 15387448]
Penttilä I, Penttilä K, Rantanen T. Laboratory diagnosis of patients with acute chest pain. Clinical chemistry and laboratory medicine. 2000 Mar:38(3):187-97 [PubMed PMID: 10905753]
Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Alexander JH, Atar D, Gersh BJ, Hanna M, Harjola VP, Horowitz JD, Husted S, Hylek EM, Lopes RD, McMurray JJ, Granger CB, ARISTOTLE Investigators. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. Journal of the American College of Cardiology. 2014 Jan 7-14:63(1):52-61. doi: 10.1016/j.jacc.2013.07.093. Epub 2013 Sep 19 [PubMed PMID: 24055845]
Level 1 (high-level) evidenceLafrenière MA, Tandon V, Ainsworth C, Nouri ', Mondoux SE, Worster A, Kavsak PA. Storage conditions, sample integrity, interferences, and a decision tool for investigating unusual high-sensitivity cardiac troponin results. Clinical biochemistry. 2023 May:115():67-76. doi: 10.1016/j.clinbiochem.2022.06.007. Epub 2022 Jun 27 [PubMed PMID: 35772501]
Canovi S, Campioli D, Marcheselli L. Specimen recentrifugation and elevated troponin I levels. Laboratory medicine. 2015 Winter:46(1):47-50. doi: 10.1309/LMPC95EL4PYEWWBR. Epub [PubMed PMID: 25617392]
Bowen RA, Remaley AT. Interferences from blood collection tube components on clinical chemistry assays. Biochemia medica. 2014:24(1):31-44. doi: 10.11613/BM.2014.006. Epub 2014 Feb 15 [PubMed PMID: 24627713]
Giavarina D, Lippi G. Blood venous sample collection: Recommendations overview and a checklist to improve quality. Clinical biochemistry. 2017 Jul:50(10-11):568-573. doi: 10.1016/j.clinbiochem.2017.02.021. Epub 2017 Feb 27 [PubMed PMID: 28242283]
Level 2 (mid-level) evidenceSimundic AM, Baird G, Cadamuro J, Costelloe SJ, Lippi G. Managing hemolyzed samples in clinical laboratories. Critical reviews in clinical laboratory sciences. 2020 Jan:57(1):1-21. doi: 10.1080/10408363.2019.1664391. Epub 2019 Oct 11 [PubMed PMID: 31603708]
Bhargava S, Singla P, Manocha A, Kankra M, Sharma A, Ahirwar A, Ralhan R, Thapliyal U, Mehra P. The Hemolyzed Sample: To Analyse Or Not To Analyse. Indian journal of clinical biochemistry : IJCB. 2020 Apr:35(2):232-238. doi: 10.1007/s12291-019-00821-4. Epub 2019 Mar 11 [PubMed PMID: 32226256]
Wang YH, Sun XF, Xu CX, Sun FQ, Wang RR, Bian XK, Wang ZZ, Wu Q. Preparation of recombinant myoglobin and investigation of the liquid antigen stability for quality control materials. Practical laboratory medicine. 2025 Apr:44():e00456. doi: 10.1016/j.plabm.2025.e00456. Epub 2025 Jan 28 [PubMed PMID: 39981498]
Level 2 (mid-level) evidenceSallach SM, Nowak R, Hudson MP, Tokarski G, Khoury N, Tomlanovich MC, Jacobsen G, de Lemos JA, McCord J. A change in serum myoglobin to detect acute myocardial infarction in patients with normal troponin I levels. The American journal of cardiology. 2004 Oct 1:94(7):864-7 [PubMed PMID: 15464666]
Srinivas VS, Cannon CP, Gibson CM, Antman EM, Greenberg MA, Tanasijevic MJ, Murphy S, de Lemos JA, Sokol S, Braunwald E, Mueller HS. Myoglobin levels at 12 hours identify patients at low risk for 30-day mortality after thrombolysis in acute myocardial infarction: a Thrombolysis in Myocardial Infarction 10B substudy. American heart journal. 2001 Jul:142(1):29-36 [PubMed PMID: 11431653]
Maalouf R, Bailey S. A review on B-type natriuretic peptide monitoring: assays and biosensors. Heart failure reviews. 2016 Sep:21(5):567-78. doi: 10.1007/s10741-016-9544-9. Epub [PubMed PMID: 26979601]
Corteville DC, Bibbins-Domingo K, Wu AH, Ali S, Schiller NB, Whooley MA. N-terminal pro-B-type natriuretic peptide as a diagnostic test for ventricular dysfunction in patients with coronary disease: data from the heart and soul study. Archives of internal medicine. 2007 Mar 12:167(5):483-9 [PubMed PMID: 17353496]
Tuegel C, Katz R, Alam M, Bhat Z, Bellovich K, de Boer I, Brosius F, Gadegbeku C, Gipson D, Hawkins J, Himmelfarb J, Ju W, Kestenbaum B, Kretzler M, Robinson-Cohen C, Steigerwalt S, Bansal N. GDF-15, Galectin 3, Soluble ST2, and Risk of Mortality and Cardiovascular Events in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2018 Oct:72(4):519-528. doi: 10.1053/j.ajkd.2018.03.025. Epub 2018 Jun 14 [PubMed PMID: 29866459]
Ay MO, Erenler AK, Dogan T, Yetim M. Diagnostic value of copeptin in acute myocardial infarction. European review for medical and pharmacological sciences. 2017 Apr:21(7):1576-1582 [PubMed PMID: 28429348]
Zhang X, Wang S, Fang S, Yu B. Prognostic Role of High Sensitivity C-Reactive Protein in Patients With Acute Myocardial Infarction. Frontiers in cardiovascular medicine. 2021:8():659446. doi: 10.3389/fcvm.2021.659446. Epub 2021 May 24 [PubMed PMID: 34109224]
Tiwari D, Aw TC. Optimizing the Clinical Use of High-Sensitivity Troponin Assays: A Review. Diagnostics (Basel, Switzerland). 2023 Dec 30:14(1):. doi: 10.3390/diagnostics14010087. Epub 2023 Dec 30 [PubMed PMID: 38201396]
LADUE JS, WROBLEWSKI F, KARMEN A. Serum glutamic oxaloacetic transaminase activity in human acute transmural myocardial infarction. Science (New York, N.Y.). 1954 Sep 24:120(3117):497-9 [PubMed PMID: 13195683]
Gao M, Cheng Y, Zheng Y, Zhang W, Wang L, Qin L. Association of serum transaminases with short- and long-term outcomes in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. BMC cardiovascular disorders. 2017 Jan 28:17(1):43. doi: 10.1186/s12872-017-0485-6. Epub 2017 Jan 28 [PubMed PMID: 28129742]
Level 2 (mid-level) evidenceLofthus DM, Stevens SR, Armstrong PW, Granger CB, Mahaffey KW. Pattern of liver enzyme elevations in acute ST-elevation myocardial infarction. Coronary artery disease. 2012 Jan:23(1):22-30. doi: 10.1097/MCA.0b013e32834e4ef1. Epub [PubMed PMID: 22113063]
Level 1 (high-level) evidenceSchmiechen NJ, Han C, Milzman DP. ED use of rapid lactate to evaluate patients with acute chest pain. Annals of emergency medicine. 1997 Nov:30(5):571-7 [PubMed PMID: 9360564]
Jialal I, Sokoll LJ. Clinical utility of lactate dehydrogenase: a historical perspective. American journal of clinical pathology. 2015 Feb:143(2):158-9. doi: 10.1309/AJCTP0FC8QFYDFA. Epub [PubMed PMID: 25596240]
Level 3 (low-level) evidenceMair J, Artner-Dworzak E, Lechleitner P, Morass B, Smidt J, Wagner I, Dienstl F, Puschendorf B. Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin. British heart journal. 1992 Nov:68(5):462-8 [PubMed PMID: 1467029]
Kost GJ, Kirk JD, Omand K. A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction. Archives of pathology & laboratory medicine. 1998 Mar:122(3):245-51 [PubMed PMID: 9823862]
Kabekkodu SP, Mananje SR, Saya RP. A Study on the Role of Heart Type Fatty Acid Binding Protein in the Diagnosis of Acute Myocardial Infarction. Journal of clinical and diagnostic research : JCDR. 2016 Jan:10(1):OC07-10. doi: 10.7860/JCDR/2016/15713.7057. Epub 2016 Jan 1 [PubMed PMID: 26894106]
Chen L, Guo X, Yang F. Role of heart-type fatty acid binding protein in early detection of acute myocardial infarction in comparison with cTnI, CK-MB and myoglobin. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 2004:24(5):449-51, 459 [PubMed PMID: 15641689]
Vupputuri A, Sekhar S, Krishnan S, Venugopal K, Natarajan KU. Heart-type fatty acid-binding protein (H-FABP) as an early diagnostic biomarker in patients with acute chest pain. Indian heart journal. 2015 Nov-Dec:67(6):538-42. doi: 10.1016/j.ihj.2015.06.035. Epub 2015 Oct 26 [PubMed PMID: 26702681]
Chin CT, Wang TY, Li S, Wiviott SD, deLemos JA, Kontos MC, Peterson ED, Roe MT. Comparison of the prognostic value of peak creatine kinase-MB and troponin levels among patients with acute myocardial infarction: a report from the Acute Coronary Treatment and Intervention Outcomes Network Registry-get with the guidelines. Clinical cardiology. 2012:35(7):424-9. doi: 10.1002/clc.21980. Epub 2012 Mar 20 [PubMed PMID: 22434769]
Level 2 (mid-level) evidenceBalk EM, Ioannidis JP, Salem D, Chew PW, Lau J. Accuracy of biomarkers to diagnose acute cardiac ischemia in the emergency department: a meta-analysis. Annals of emergency medicine. 2001 May:37(5):478-94 [PubMed PMID: 11326184]
Level 1 (high-level) evidenceAydin S, Ugur K, Aydin S, Sahin İ, Yardim M. Biomarkers in acute myocardial infarction: current perspectives. Vascular health and risk management. 2019:15():1-10. doi: 10.2147/VHRM.S166157. Epub 2019 Jan 17 [PubMed PMID: 30697054]
Level 3 (low-level) evidenceSharma S, Jackson PG, Makan J. Cardiac troponins. Journal of clinical pathology. 2004 Oct:57(10):1025-6 [PubMed PMID: 15452153]
Chauin A. The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis. Vascular health and risk management. 2021:17():601-617. doi: 10.2147/VHRM.S327661. Epub 2021 Sep 21 [PubMed PMID: 34584417]
Pabón AMC, Pyles E, Peach D, Ahmad S, O'Brien PB, Kuhlman M, Steiner S, Crown L, Purinton E, Priano J. Implementation of High-Sensitivity Troponin for Early Rule-Out of Acute Myocardial Infarction in Emergency Department. American journal of medicine open. 2025 Dec:14():100103. doi: 10.1016/j.ajmo.2025.100103. Epub 2025 May 15 [PubMed PMID: 40607172]
Domienik-Karłowicz J, Kupczyńska K, Michalski B, Kapłon-Cieślicka A, Darocha S, Dobrowolski P, Wybraniec M, Wańha W, Jaguszewski M. Fourth universal definition of myocardial infarction. Selected messages from the European Society of Cardiology document and lessons learned from the new guidelines on ST-segment elevation myocardial infarction and non-ST-segment elevation-acute coronary syndrome. Cardiology journal. 2021:28(2):195-201. doi: 10.5603/CJ.a2021.0036. Epub 2021 Apr 12 [PubMed PMID: 33843035]
Kanyal S, Das A, Bashir AMD, Syed AH, Aujla S, Chaudhary J, Patel D, Goel A. N‑Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) as a Biomarker in Heart Failure With Preserved Ejection Fraction (HFpEF) Versus Heart Failure With Reduced Ejection Fraction (HFrEF): The Way Forward in the Age of Proteomics. Cureus. 2025 Oct:17(10):e94162. doi: 10.7759/cureus.94162. Epub 2025 Oct 8 [PubMed PMID: 41209853]
Möckel M, Searle J. Copeptin-marker of acute myocardial infarction. Current atherosclerosis reports. 2014 Jul:16(7):421. doi: 10.1007/s11883-014-0421-5. Epub [PubMed PMID: 24844208]
Patel DM, Thiessen-Philbrook H, Brown JR, McArthur E, Moledina DG, Mansour SG, Shlipak MG, Koyner JL, Kavsak P, Whitlock RP, Everett AD, Malenka DJ, Garg AX, Coca SG, Parikh CR. Association of plasma-soluble ST2 and galectin-3 with cardiovascular events and mortality following cardiac surgery. American heart journal. 2020 Feb:220():253-263. doi: 10.1016/j.ahj.2019.11.014. Epub 2019 Dec 3 [PubMed PMID: 31911262]
Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ, Donahue MP, Kitzman DW, Piña IL, Zannad F, Kraus WE, O'Connor CM, Felker GM. Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure: Insights From the HF-ACTION Study. JACC. Heart failure. 2017 Oct:5(10):724-734. doi: 10.1016/j.jchf.2017.07.013. Epub [PubMed PMID: 28958347]
Wang Z, Tang J, Shi Q, Fang L, Liu N, Zhang J. Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: a large prospective cohort study. Frontiers in endocrinology. 2024:15():1392859. doi: 10.3389/fendo.2024.1392859. Epub 2024 May 15 [PubMed PMID: 38812817]
Tilea I, Varga A, Serban RC. Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction-Promises and Challenges. Diagnostics (Basel, Switzerland). 2021 May 15:11(5):. doi: 10.3390/diagnostics11050881. Epub 2021 May 15 [PubMed PMID: 34063483]
Clerico A, Zaninotto M, Passino C, Padoan A, Migliardi M, Plebani M. High-sensitivity methods for cardiac troponins: The mission is not over yet. Advances in clinical chemistry. 2021:103():215-252. doi: 10.1016/bs.acc.2020.08.009. Epub 2020 Oct 9 [PubMed PMID: 34229851]
Level 3 (low-level) evidenceClerico A, Zaninotto M, Padoan A, Masotti S, Musetti V, Prontera C, Ndreu R, Zucchelli G, Passino C, Migliardi M, Plebani M. Evaluation of analytical performance of immunoassay methods for cTnI and cTnT: From theory to practice. Advances in clinical chemistry. 2019:93():239-262. doi: 10.1016/bs.acc.2019.07.005. Epub 2019 Aug 27 [PubMed PMID: 31655731]
Level 3 (low-level) evidenceMatveeva E, Gryczynski Z, Gryczynski I, Malicka J, Lakowicz JR. Myoglobin immunoassay utilizing directional surface plasmon-coupled emission. Analytical chemistry. 2004 Nov 1:76(21):6287-92 [PubMed PMID: 15516120]
Stone MJ, Willerson JT, Gomez-Sanchez CE, Waterman MR. Radioimmunoassay of myoglobin in human serum. Results in patients with acute myocardial infarction. The Journal of clinical investigation. 1975 Nov:56(5):1334-9 [PubMed PMID: 1184754]
Hudson MP, Christenson RH, Newby LK, Kaplan AL, Ohman EM. Cardiac markers: point of care testing. Clinica chimica acta; international journal of clinical chemistry. 1999 Jun 30:284(2):223-37 [PubMed PMID: 10451248]
Kim Y, Kim H, Kim SY, Lee HK, Kwon HJ, Kim YG, Lee J, Kim HM, So BH. Automated heart-type fatty acid-binding protein assay for the early diagnosis of acute myocardial infarction. American journal of clinical pathology. 2010 Jul:134(1):157-62. doi: 10.1309/AJCP0F6AXRCJMQQG. Epub [PubMed PMID: 20551280]
Jaiswal A, Vamne A, Verma MK, Doctor B. H-FABP as a diagnostic marker for early detection of young myocardial infarction among Indians. Bioinformation. 2022:18(6):506-512. doi: 10.6026/97320630018506. Epub 2022 Jun 30 [PubMed PMID: 37168777]
Tamm NN, Semenov AG, Seferian KR, Bereznikova AV, Murakami MM, Apple FS, Koshkina EV, Krasnoselsky MI, Katrukha AG. Measurement of B-type natriuretic peptide by two assays utilizing antibodies with different epitope specificity. Clinical biochemistry. 2011 Feb:44(2-3):257-9. doi: 10.1016/j.clinbiochem.2010.09.030. Epub 2010 Oct 13 [PubMed PMID: 20950595]
Alawieh H, Chemaly TE, Alam S, Khraiche M. Towards Point-of-Care Heart Failure Diagnostic Platforms: BNP and NT-proBNP Biosensors. Sensors (Basel, Switzerland). 2019 Nov 16:19(22):. doi: 10.3390/s19225003. Epub 2019 Nov 16 [PubMed PMID: 31744130]
Cui Y, Qi X, Huang A, Li J, Hou W, Liu K. Differential and Predictive Value of Galectin-3 and Soluble Suppression of Tumorigenicity-2 (sST2) in Heart Failure with Preserved Ejection Fraction. Medical science monitor : international medical journal of experimental and clinical research. 2018 Jul 24:24():5139-5146. doi: 10.12659/MSM.908840. Epub 2018 Jul 24 [PubMed PMID: 30039808]
Level 2 (mid-level) evidenceKato ET, Morrow DA, Guo J, Berg DD, Blazing MA, Bohula EA, Bonaca MP, Cannon CP, de Lemos JA, Giugliano RP, Jarolim P, Kempf T, Kristin Newby L, O'Donoghue ML, Pfeffer MA, Rifai N, Wiviott SD, Wollert KC, Braunwald E, Sabatine MS. Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis. European heart journal. 2023 Jan 21:44(4):293-300. doi: 10.1093/eurheartj/ehac577. Epub [PubMed PMID: 36303404]
Level 1 (high-level) evidenceMaisel A, Mueller C, Neath SX, Christenson RH, Morgenthaler NG, McCord J, Nowak RM, Vilke G, Daniels LB, Hollander JE, Apple FS, Cannon C, Nagurney JT, Schreiber D, deFilippi C, Hogan C, Diercks DB, Stein JC, Headden G, Limkakeng AT Jr, Anand I, Wu AHB, Papassotiriou J, Hartmann O, Ebmeyer S, Clopton P, Jaffe AS, Peacock WF. Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction). Journal of the American College of Cardiology. 2013 Jul 9:62(2):150-160. doi: 10.1016/j.jacc.2013.04.011. Epub 2013 Apr 30 [PubMed PMID: 23643595]
Saeedi R, Frohlich J. Lipoprotein (a), an independent cardiovascular risk marker. Clinical diabetes and endocrinology. 2016:2():7. doi: 10.1186/s40842-016-0024-x. Epub 2016 Mar 31 [PubMed PMID: 28702242]
Ebrahimi S, Alivirdiloo V, Hajiabbasi M, Masoumi S, Mohammadi M, Hosseini S, Gargari SO, Mobed A. Cardiac Troponin I Biosensors: Innovations in Real-Time Diagnosis of Cardiovascular Diseases. Analytical science advances. 2025 Jun:6(1):e70009. doi: 10.1002/ansa.70009. Epub 2025 Apr 1 [PubMed PMID: 40177114]
Level 3 (low-level) evidenceRujic D, Pareek M, Egholm G, Thygesen K. [Clinical considerations in the interpretation of elevated troponin levels]. Ugeskrift for laeger. 2015 Feb 9:177(7):. pii: V11140589. Epub [PubMed PMID: 25697072]
Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart (British Cardiac Society). 2006 Jul:92(7):987-93 [PubMed PMID: 16775113]
Kurapati R, Zubair M. Creatine Kinase MB: Diagnostic Utility and Limitations. StatPearls. 2026 Jan:(): [PubMed PMID: 32491523]
Kwon HJ, Seo EJ, Min KO. The influence of hemolysis, turbidity and icterus on the measurements of CK-MB, troponin I and myoglobin. Clinical chemistry and laboratory medicine. 2003 Mar:41(3):360-4 [PubMed PMID: 12705347]
Goel H, Melot J, Krinock MD, Kumar A, Nadar SK, Lip GYH. Heart-type fatty acid-binding protein: an overlooked cardiac biomarker. Annals of medicine. 2020 Dec:52(8):444-461. doi: 10.1080/07853890.2020.1800075. Epub 2020 Aug 4 [PubMed PMID: 32697102]
Jones NR, Taylor KS, Ordóñez-Mena JM, Goyder CR, Hobbs FDR, Taylor CJ. NT-proBNP testing for heart failure diagnosis in people with atrial fibrillation: A diagnostic accuracy study. PLoS medicine. 2025 Oct:22(10):e1004550. doi: 10.1371/journal.pmed.1004550. Epub 2025 Oct 30 [PubMed PMID: 41166233]
Mu D, Ma C, Cheng J, Zou Y, Qiu L, Cheng X. Copeptin in fluid disorders and stress. Clinica chimica acta; international journal of clinical chemistry. 2022 Apr 1:529():46-60. doi: 10.1016/j.cca.2022.02.002. Epub 2022 Feb 7 [PubMed PMID: 35143773]
Level 2 (mid-level) evidenceMoodley N. Copeptin analysis in endocrine disorders. Frontiers in endocrinology. 2023:14():1230045. doi: 10.3389/fendo.2023.1230045. Epub 2023 Oct 4 [PubMed PMID: 37859988]
Zaninotto M, Pagani F, Altinier S, Amboni P, Bonora R, Dolci A, Pergolini P, Vernocchi A, Plebani M, Panteghini M. Multicenter evaluation of five assays for myoglobin determination. Clinical chemistry. 2000 Oct:46(10):1631-7 [PubMed PMID: 11017942]
Greenson JK, Farber SJ, Dubin SB. The effect of hemolysis on creatine kinase determination. Archives of pathology & laboratory medicine. 1989 Feb:113(2):184-5 [PubMed PMID: 2916906]
Galli C, Lippi G. High-sensitivity cardiac troponin testing in routine practice: economic and organizational advantages. Annals of translational medicine. 2016 Jul:4(13):257. doi: 10.21037/atm.2016.07.04. Epub [PubMed PMID: 27500158]
Rao SV, O'Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, Baber U, Baker H, Cohen MG, Cruz-Ruiz M, Davis LL, de Lemos JA, DeWald TA, Elgendy IY, Feldman DN, Goyal A, Isiadinso I, Menon V, Morrow DA, Mukherjee D, Platz E, Promes SB, Sandner S, Sandoval Y, Schunder R, Shah B, Stopyra JP, Talbot AW, Taub PR, Williams MS. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025 Apr:151(13):e771-e862. doi: 10.1161/CIR.0000000000001309. Epub 2025 Feb 27 [PubMed PMID: 40014670]
Level 1 (high-level) evidenceBabuin L, Jaffe AS. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2005 Nov 8:173(10):1191-202 [PubMed PMID: 16275971]
Maimaitiming M, Li S, Huang K, Maimaitiming M, Liu F, Smith SC, Zheng ZJ, Jin Y. Risk factors for cardiogenic shock incidence and mortality after acute myocardial infarction: a systematic review and meta-analysis. Communications medicine. 2025 May 27:5(1):200. doi: 10.1038/s43856-025-00874-y. Epub 2025 May 27 [PubMed PMID: 40425745]
Level 1 (high-level) evidencevan Beek D, van Zaane B, Looije M, Peelen L, van Klei W. Typical rise and fall of troponin in (peri-procedural) myocardial infarction: A systematic review. World journal of cardiology. 2016 Mar 26:8(3):293-301. doi: 10.4330/wjc.v8.i3.293. Epub [PubMed PMID: 27022461]
Level 1 (high-level) evidenceStorrow AB, Nowak RM, Diercks DB, Singer AJ, Wu AH, Kulstad E, LoVecchio F, Fromm C, Headden G, Potis T, Hogan CJ, Schrock JW, Zelinski DP, Greenberg MR, Christenson RH, Ritchie JC, Chamberlin JS, Bray KR, Rhodes DW, Trainor D, Southwick PC. Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: Results of a prospective multicenter trial. Clinical biochemistry. 2015 Mar:48(4-5):260-7. doi: 10.1016/j.clinbiochem.2014.09.012. Epub 2014 Sep 28 [PubMed PMID: 25261587]
Level 1 (high-level) evidenceCao Z, Jia Y, Zhu B. BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. International journal of molecular sciences. 2019 Apr 12:20(8):. doi: 10.3390/ijms20081820. Epub 2019 Apr 12 [PubMed PMID: 31013779]
AlSadah K, S El-Masry O, Alzahrani F, Alomar A, Ghany MA. Reporting Clinical Laboratory Critical Values: A Focus On The Recommendations Of The American College Of Pathologists. Journal of Ayub Medical College, Abbottabad : JAMC. 2019 Oct-Dec:31(4):612-618 [PubMed PMID: 31933321]
Chaulin AM. Cardiac Troponins Metabolism: From Biochemical Mechanisms to Clinical Practice (Literature Review). International journal of molecular sciences. 2021 Oct 10:22(20):. doi: 10.3390/ijms222010928. Epub 2021 Oct 10 [PubMed PMID: 34681585]
Kavsak PA, Worster A, Ma J, Shortt C, Clayton N, Sherbino J, Hill SA, McQueen M, Mehta SR, Devereaux PJ. High-Sensitivity Cardiac Troponin Risk Cutoffs for Acute Cardiac Outcomes at Emergency Department Presentation. The Canadian journal of cardiology. 2017 Jul:33(7):898-903. doi: 10.1016/j.cjca.2017.04.011. Epub 2017 May 3 [PubMed PMID: 28668141]
McErlean ES, Deluca SA, van Lente F, Peacock F 4th, Rao JS, Balog CA, Nissen SE. Comparison of troponin T versus creatine kinase-MB in suspected acute coronary syndromes. The American journal of cardiology. 2000 Feb 15:85(4):421-6 [PubMed PMID: 10728944]
Mueller C, Möckel M, Giannitsis E, Huber K, Mair J, Plebani M, Thygesen K, Jaffe AS, Lindahl B, ESC Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association. Use of copeptin for rapid rule-out of acute myocardial infarction. European heart journal. Acute cardiovascular care. 2018 Sep:7(6):570-576. doi: 10.1177/2048872617710791. Epub 2017 Jun 8 [PubMed PMID: 28593800]
Chan D, Ng LL. Biomarkers in acute myocardial infarction. BMC medicine. 2010 Jun 7:8():34. doi: 10.1186/1741-7015-8-34. Epub 2010 Jun 7 [PubMed PMID: 20529285]
Howanitz PJ, Howanitz JH. Quality control for the clinical laboratory. Clinics in laboratory medicine. 1983 Sep:3(3):541-51 [PubMed PMID: 6357609]
Level 2 (mid-level) evidenceKinns H, Pitkin S, Housley D, Freedman DB. Internal quality control: best practice. Journal of clinical pathology. 2013 Dec:66(12):1027-32. doi: 10.1136/jclinpath-2013-201661. Epub 2013 Sep 26 [PubMed PMID: 24072731]
Level 2 (mid-level) evidenceKearney E. Internal quality control. Methods in molecular biology (Clifton, N.J.). 2013:1065():277-89. doi: 10.1007/978-1-62703-616-0_18. Epub [PubMed PMID: 23996371]
Level 2 (mid-level) evidenceWestgard JO. A Total Quality-Control Plan with Right-Sized Statistical Quality-Control. Clinics in laboratory medicine. 2017 Mar:37(1):137-150. doi: 10.1016/j.cll.2016.09.011. Epub 2016 Dec 20 [PubMed PMID: 28153361]
Level 2 (mid-level) evidenceWestgard JO. Internal quality control: planning and implementation strategies. Annals of clinical biochemistry. 2003 Nov:40(Pt 6):593-611 [PubMed PMID: 14629798]
Level 2 (mid-level) evidenceBayat H. Selecting multi-rule quality control procedures based on patient risk. Clinical chemistry and laboratory medicine. 2017 Oct 26:55(11):1702-1708. doi: 10.1515/cclm-2016-1077. Epub [PubMed PMID: 28236626]
Level 2 (mid-level) evidenceTopic E, Nikolac N, Panteghini M, Theodorsson E, Salvagno GL, Miler M, Simundic AM, Infusino I, Nordin G, Westgard S. How to assess the quality of your analytical method? Clinical chemistry and laboratory medicine. 2015 Oct:53(11):1707-18. doi: 10.1515/cclm-2015-0869. Epub [PubMed PMID: 26408611]
Level 2 (mid-level) evidenceDalenberg DA, Schryver PG, Klee GG. Analytical performance specifications: relating laboratory performance to quality required for intended clinical use. Clinics in laboratory medicine. 2013 Mar:33(1):55-73. doi: 10.1016/j.cll.2012.11.005. Epub 2012 Dec 20 [PubMed PMID: 23331729]
Level 2 (mid-level) evidenceBadrick T. Integrating quality control and external quality assurance. Clinical biochemistry. 2021 Sep:95():15-27. doi: 10.1016/j.clinbiochem.2021.05.003. Epub 2021 May 7 [PubMed PMID: 33965412]
Level 2 (mid-level) evidenceCenters for Disease Control and Prevention (CDC) (2) Centers for Medicare & Medicaid Services (CMS), HHS. Medicare, Medicaid, and CLIA programs; laboratory requirements relating to quality systems and certain personnel qualifications. Final rule. Federal register. 2003 Jan 24:68(16):3639-714 [PubMed PMID: 12545998]
Level 2 (mid-level) evidenceRojo-Molinero E, Alados JC, de la Pedrosa EG, Leiva J, Pérez JL. [Safety in the Microbiology laboratory]. Enfermedades infecciosas y microbiologia clinica. 2015 Jun-Jul:33(6):404-10. doi: 10.1016/j.eimc.2014.06.014. Epub 2014 Nov 8 [PubMed PMID: 25444041]
Level 3 (low-level) evidenceLo J. Biological safety in the medical laboratory. Hong Kong medical journal = Xianggang yi xue za zhi. 2015 Jun:21(3):200. doi: 10.12809/hkmj154581. Epub [PubMed PMID: 26045068]